USOO5958975A United States Patent (19) 11 Patent Number: 5,958,975 Yu et al. (45) Date of Patent: *Sep. 28, 1999

4,246.261 1/1981 Van Scott et al...... 514/171

54). ANTIODOR, ANTIMICROBIAL AND PRESERVATIVE COMPOSITIONS AND 4,363,815 12/1982 Yu et al...... 514/263 METHODS OF USING SAME 4,518,789 5/1985 Yu et al...... 514/554 5,258,391 11/1993 Van Scott et al...... 514/529 75 Inventors: Ruey J. Yu, Ambler; Eugene J. Van 5,641,475 6/1997 Yu et al...... 424/65 Scott, Abington, both of Pa. 5,643,949 7/1997 Van Scott et al...... 514/533 OTHER PUBLICATIONS 73 Assignee: Tristrata, Inc., Princeton, N.J. Current Therapy, p. 662 (1981). * Notice: This patent is Subject to a terminal dis Current Therapy, pp. 599–603 (1984). claimer. The Merck Index, 9th Ed., Abstract 7961 (1976). Haines Ely, M.D., “Dermatologic Therapies You’ve Prob 21 Appl. No.: 09/164,005 ably Never Heard Of", Dermatologic Clinics, vol. 7, No. 1, pp. 19-35 (Jan. 1989). 22 Filed: Sep. 30, 1998 Primary Examiner Jose' G. Dees Related U.S. Application Data ASSistant Examiner Michael A. Williamson Attorney, Agent, or Firm Panitch Schwarze Jacobs & 62 Division of application No. 09/107.872, Jun. 30, 1998, Pat. Nadel, P.C. No. 5,874,071, which is a division of application No. 08/807,859, Feb. 26, 1997, Pat. No. 5,807,890, which is a 57 ABSTRACT division of application No. 08/333,159, Nov. 1, 1994, Pat. No. 5,641,475, which is a continuation-in-part of application Therapeutic treatment as well as prophylactic measures are No. 08/276.275, Jul.18, 1994, Pat. No. 5,643,949, which is provided by topical application of compositions containing a division of application No. 08/132,837, Oct. 7, 1993, abandoned, which is a division of application No. 07/630, an aryl 2-acetoxyethanoic acid to eradicate or prevent the 743, Dec. 20, 1990, Pat. No. 5,258,391, which is a continu development of axillary foul odor, foot malodor and other ation of application No. 07/266,702, Nov. 3, 1988, aban body odors, e.g. Scalp, and Skin, nail and follicular infections doned, which is a continuation of application No. 07/050, caused by microorganisms. The compositions are antimi 143, May 15, 1987, abandoned. crobial against Several organisms that infect the skin and are (51) Int. Cl...... A61K 31/185 Specifically effective against P. acnes. The compositions are 52 U.S. Cl...... 514/553; 514/529; 514/532; therapeutically effective against folliculitis and perifollicu 514/546; 514/548; 514/553; 514/557; 514/568 litis and are useful for other skin lesions, nail and mucosal infections Such as impetigo, Seborrheic dermatitis, erythr 58 Field of Search ...... 514/533, 529, asma and trichomycosis axillaris, associated with or caused 514/532, 546, 548,553, 557, 568; 424/59, by microorganisms. The therapeutic effect of the composi 60, 70.1 tion may be Synergized or amplified by incorporating a 56) References Cited cosmetic or dermatologic agent into the formulation for topical treatment of cosmetic and dermatologic indications. U.S. PATENT DOCUMENTS The compositions are also useful as preservatives in food 3,879,537 4/1975 Van Scott et al...... 514/460 products, cosmetic and pharmaceutical formulations, and 3,920,835 11/1975 Van Scott et al. ... 514/460 industrial preparations. 4,105,783 8/1978 Yu et al...... 514/489 4,216,224 8/1980 Yu et al...... 560/128 8 Claims, No Drawings 5,958,975 1 2 ANTIODOR, ANTIMICROBIAL AND include aluminum chloride, aluminum chlorhydroxide, alu PRESERVATIVE COMPOSITIONS AND minum Sulfate, aluminum potassium Sulfate and aluminum METHODS OF USING SAME phenolsulfonate. The Zinc Salts comprise Zinc oxide, Zinc peroxide, Zinc Stearate and Zinc phenolsulfonate. CROSS-REFERENCE TO RELATED Although long-term use of aluminum or Zinc Salts as APPLICATIONS underarm deodorants presents no major problems in toxicity, This is a division of application Ser. No. 09/107.872, filed those compounds do frequently cause irritation, burning, Jun. 30, 1998, which is a division of application Ser. No. itching and other uncomfortable Sensations to Some people 08/807,859, filed Feb. 26, 1997, now U.S. Pat. No. 5,807, with Sensitive skin. These people Stop using underarm 890, which is a division of application Ser. No. 08/333,159, deodorants commonly available on the market today filed Nov. 1, 1994, now U.S. Pat. No. 5,641,475, which is a because of persistentitching or burning after use. Moreover, continuation-in-part of our copending application Ser. No. Such irritation, burning and itching caused by underarm 08/276,275, filed Jul. 18, 1994, now U.S. Pat. No. 5,693, deodorants makes them even less Suitable for application to 949, which is a division of application Ser. No. 08/132,837, other areas of the body which are even more sensitive than filed Oct. 7, 1993, now abandoned, which is a division of 15 the underarm. Development of other efficacious anti-odorant application Ser. No. 07/630,743, filed Dec. 20, 1990, now Substances which do not cause irritation or uncomfortable U.S. Pat. No. 5,258,391, which is a continuation of appli Sensation when applied to the Skin is therefore desirable. cation Ser. No. 07/266,702, filed Nov. 3, 1988, now Nail infections may be caused by gram-positive bacteria abandoned, which is a continuation of application Ser. No. Such as StaphylococcuS aureus and StreotOCOccus pyogenes; 07/050,143, filed May 15, 1987, now abandoned. gram-negative bacteria Such as Pseudomonas aeruginosa; dermatophytes such as Trichophyton rubrum and Trichophy FIELD OF THE INVENTION ton mentagrophytes, yeasts Such as Candida albicans or The invention relates to antiodor, antimicrobial and pre herpes simplex virus. In general, nail infections are difficult Servative compositions for prophylactic measures as well as to treat by topical application, because most commercially topical treatment of Skin foul odor and infections caused by 25 available products are not formulated in bioavailable form to microorganisms. More particularly, the invention is directed penetrate the hard nail plate. to compositions useful for topical application to treat and to Mucocutaneous integuments include for example oral prevent the development of axillary foul odor, foot malodor mucosa, Vaginal mucosa and anogenital areas. Although and other body foul odor, and to alleviate skin disorders infections may be caused by bacteria, the most common asSociated with microbial infections, and also useful as forms are due to Candida yeasts and herpes virus. Vulvar preservatives in food products and cosmetic and pharma vaginal infections may be caused for example by Staphylo ceutical formulations. coccuS aureus, Pseudomonas aeruginosa, Candida albicans, Trichomonas vaginalis, Gardnerella vaginalis, BACKGROUND OF THE INVENTION 35 Corynebacterium minutissimum or herpes simplex Type I or In human skin, Sebaceous glands, eccrine Sweat glands Type II virus. The yeast infections are usually treated with and apocrine glands Secrete various chemicals onto the skin butaconazole, clotrimazole, terconazole or miconazole Surface. These chemicals include Sodium chloride, potas cream for 3 to 7 days. The bacterial infections may be treated sium bicarbonate, lactic acid, urea, Squalene, proteins, with oral administration of metronidazole 500 mg or clin carbohydrates, triglycerides and other lipids. Although body 40 damycin 300 mg twice daily for 7 days. For herpes odor may be partially due to certain chemicals Secreted by infections, oral administration of acyclovir 200 mg 5 times Sebaceous glands and eccrine Sweat glands, major axillary daily for 10 days or topical application of 5% acyclovir foul odor is due to Secretions of the apocrine glands, which ointment may be prescribed with various degrees of effec contain special nutrient materials for microorganisms. tiveness. Apocrine glands are located primarily in the axillae, 45 Folliculitis and perifolliculitis are inflammatory disorders anogenital region, mammary areolae, ear canals, eyelids, within or around the hair follicle, often caused by pathogenic and are Scattered on parts of the face, anterior chest and bacteria or other microorganisms. The microorganisms may abdomen. In general, the apocrine duct opens into the upper include StaphylococcuS aureus, Pseudomonas aeruginosa, end of the hair follicle although it may occasionally open and Propionibacterium acneS. In most cases, Scalp, face, directly onto the Skin Surface. In contrast to the eccrine 50 chest, back and lower legs are involved. Folliculitis and glands, which produce a clear watery liquid, the apocrine perifolliculitis may be Superficial infections and appear as glands Secrete a milky fluid that has a pH range of 5 to 6.5 Small pustules in or around hair follicles. However, deeper and initially consists of lipids, proteins and carbohydrates. infections may include lesions of papules and nodules. Although fresh apocrine Secretions do not have an objec Patients may feel Slight burning, itching and pain in the tionable odor, the Secreted compounds are found to undergo 55 infected areas. Folliculitis may be persistent and last for decomposition by both chemical and microbial actions, and months and even years. Topical application of mupirocin, the degradation products are responsible for the offensive chlorhexidine or aluminum chloride appears to be helpful odors. Chemical Substances identified as contributing to this and effective in many instances. unpleasant odor include lower organic acids Such as In our U.S. Pat. No. 4,363,815, entitled “Alpha butanoic, isopentanoic, hexanoic and octanoic acids, mer 60 Hydroxyacids, Alpha Ketoacids and Their Use in Treating captains, indoles, amines, hydrogen Sulfide; ammonia; and Skin Conditions', we described and claimed that certain phosphine. Although gram-positive bacteria, thriving on alpha hydroxyacids and related compounds are therapeuti Substances found on the moist skin Surface, appear to be cally effective for topical treatment of skin disorders asso responsible for the production of malodor, the precise ciated with disturbed keratinization or inflammation. Such mechanisms of odor production are Still unclear. 65 skin disorders include dry skin, ichthyosis, palmar and Most deodorant or antiperspirant products on the market plantar hyperkeratosis, dandruff, Darier's disease, lichen today are Salts of aluminum or zinc. The aluminum Salts Simplex chronicus, keratoses, acne, psoriasis, eczema, pru 5,958,975 3 4 ritus and possibly warts and herpes. The alpha hydroxyacids Since R and R may both be aryl groups, the invention and related compounds disclosed in the patent include includes the use of both aryl and diaryl 2-acetoxyethanoic phenyl 2-acetoxyethanoic acid (also known as phenyl alpha acids, but for ease of reference the compounds of formula (I) acetoxyacetic acid or O-acetylmandelic acid) which is a will be simply referred to herein as aryl 2-acetoxyethanoic derivative compound formed by acetylation of the hydroxy acids. Aryl 2-acetoxyethanoic acids may also exist as Ste group of mandelic acid. reoisomerS Such as D, L, and DL forms when R and R2 are In our U.S. Pat. No. 5,258,391, entitled “Phenyl Alpha not identical. Aryl 2-acetoxyethanoic acids may also be Acyloxyalkanoic Acids, Derivatives and Their Therapeutic present as a free acid or a Salt form with an inorganic or Use', we disclosed and claimed compositions containing organic base. these compounds for topical application to promote growth Representative aryl 2-acetoxyethanoic acids include but and hardening of nails and hair, wound healing and thick are not limited to the following: phenyl 2-acetoxyethanoic ening of mucous membranes, skin and its appendages. acid, (wherein in formula I: R=CHS, R=H); diphenyl However, compositions containing phenyl or diphenyl 2-acetoxyethanoic acid, (wherein R=CHS, R=CHs) 2-acetoxyethanoic acid or their aryl or diaryl analogs have (4-methylphenyl) 2-acetoxyethanoic acid, (wherein not previously been disclosed to be effective and useful for 15 R = CHCH, R = H); (4-hydroxyphenyl) topical application to alleviate skin infections and body foul 2-acetoxyethanoic acid, (wherein R=HOCH, R=H); odor caused by one or more microorganisms. (4-chlorophenyl) 2-acetoxyethanoic acid, (where in R=CICH, R=H); (2-chlorophenyl) 2-acetoxyethanoic BRIEF SUMMARY OF THE INVENTION acid, (wherein R=CICH, R=H); (4-acetoxyphenyl) According to the present invention, it has been found that 2-acetoxyethanoic acid, (wherein R=CHCOOCH, aryl or diaryl 2-acetoxyethanoic acids, when topically R = H); (4-chlorophenyl) (2-chlorophenyl) applied to body parts, Such as the human axillae, foot or 2-acetoxyethanoic acid, (where in R = ClC6H, Scalp, are useful in preventing and/or treating body foul R=ClCH); (4-methylphenyl) (2-chlorophenyl) odor. Further, according to the invention, it has been found 2-acetoxyethanoic acid, (where in R = CHCH, that the topical application of aryl or diaryl 25 R=CICH); and (2-Naphthyl) 2-acetoxyethanoic acid, 2-acetoxyethanoic acids to the skin, nails and mucosal (wherein R=CH7, R=H). Preferred aryl and diary1 membranes is therapeutically effective to eradicate or Sub 2-acetoxyethanoic acids include but are not limited to the Stantially improve Skin lesions, Such as folliculitis, following: phenyl 2-acetoxyethanoic acid, diphenyl perifolliculitis, impetigo, dandruff, Seborrheic dermatitis, 2-acetoxyethanoic acid; (4-chlorophenyl) 2-acetoxyethanoic erythrasma and trichomycosis axillaris, and nail infections acid; (2-chlorophenyl) 2-acetoxyethanoic acid; and and mucosal infections, including oral infections and vagi (4-chlorophenyl) (2-chlorophenyl) 2-acetoxyethanoic acid. nal infections caused by various microorganisms. Further Skin infections are generally caused by microbial agents Still, aryl or diaryl 2-acetoxyethanoic acids are useful as which include bacteria, yeasts, fungi and viruses. It now preservatives in food products, cosmetic and pharmaceutical appears that the aryl 2-acetoxyethanoic acids may have cidal formulations and industrial preparations. 35 as well as Static effects, i.e., killing as well as inhibiting the The aryl or diaryl 2-acetoxyethanoic acids may be applied growth of microorganisms. These compounds can thus treat in various formulations Such as Solutions, gels, creams, the infections as well as alleviating the Symptoms thereof. lotions, Stick, balm, Sprays or powders in either anhydrous We have now discovered that aryl 2-acetoxyethanoic or aqueous vehicles. In addition, the compositions contain acids have unexpected, much broader therapeutic utility than ing an aryl or diaryl 2-acetoxyethanoic acid may be formu 40 previously described. Under standard microbial tests, this lated or applied contemporaneously with other topical compound has been found to inhibit the growth of various agents to provide Synergistic or amplified activity for coS bacteria including StaphylococcuS aureus, StaphylococcuS metic or dermatologic indications of the body part being epidermidis, MicrococcuS Sedentarius, MicrococcuS luteus, treated. Brevibacterium epidermis, Corynebaccerium minutissium, 45 Serratia marceScens, Pseudomonas aeruginosa, Escheri DETAILED DESCRIPTION OF PREFERRED chia coli, and Propionibacterium acnes. EMBODIMENTS Aryl 2-acetoxyethanoic acid is Specifically effective against the growth of P. acnes even in the presence of 10% In accordance with the present invention aryl or diaryl lipid material in the test media. The inhibitory effect against 2-acetoxyethanoic acids which may be incorporated into 50 P. acnes of this compound has been found to be greater than topical compositions for body foul odor, skin, nail and that of benzoyl peroxide under the same test conditions. mucosal infections and related dermatologic disorders or Commonly used antiseptic compounds chlorhexidine glu into food products, cosmetic or pharmaceutical formulations conate and triclosan have been tested and compared under or industrial preparations as preservatives therefor, are the same conditions and were found to be effective against shown by the following chemical structural formula 55 various bacteria in the absence of lipid materials. However, chlorhexidine gluconate and tricloSan have been found to be (I) ineffective against most microorganisms when lipid mate O O || || rials are incorporated into the test media. In Skin lesions, RRC(OCCH3)COH Such as folliculitis, lipid materials including Sebum Secreted 60 by Sebaceous glands are present. In contrast to these two compounds, aryl 2-acetoxyethanoic acid has been found to wherein R=an aryl group having 6 to 13 carbon atoms, and be very effective against P. acnes even in the presence of R=H or an aryl group having 6 to 13 carbon atoms. The lipid materials, particularly in treating and preventing the hydrogen atoms of the aryl groups may be Substituted by an Spread of acne Vulgaris. element or group Such as F, Cl, Br, I, OH, AcO (acetoxy) or 65 We have now discovered that a composition containing a Saturated or unsaturated radical having 1 to 9 carbon aryl 2-acetoxyethanoic acid is topically effective in prevent atoms, Such as a lower alkyl or alkoxy. ing the development of, as well as in treating, body foul 5,958,975 S 6 odor. Specifically, the composition is useful for topical hydroxy Zine, terbinafine, diphenhydramine, lidocaine, application to prevent the development of axillary foul odor procaine, mepivacaine, monobenzone, erythromycin, and foot malodor. The composition is also therapeutically tetracycline, clindamycin, meclocycline, hydroquinone, effective for topical treatment of underarm foul odor and minocycline, naproxen, ibuprofen, theophylline, cromolyn, foot malodor. retinoic acid, 13-cis retinoic acid, hydrocortisone, hydrocor We have also discovered that the compositions are useful tisone 21-acetate, hydrocortisone 17-Valerate, hydrocorti for topical application to eradicate or Substantially improve Sone 17-butyrate, betamethasome Valerate, betamethasone skin lesions Such as folliculitis, perifolliculitis, impetigo, dipropionate, triamcinolone acetonide, fluocinonide, dandruff, Seborrheic dermatitis, erythrasma and trichomy clobetasol, propionate, benzoyl peroxide, hydrogen cosis axillaris, and nail infections and mucosal infections peroxide, crotamiton, propranolol, promethazine, Vitamin A including oral infections and vaginal infections caused by palmitate, Vitamin A acetate, and Vitamin E acetate. microbial organisms. These microorganisms include Sta For example, treatment for nail infections may include phylococcuS Species Such as S. aureus and S. epidermis; compositions containing an aryl 2-acetoxyethanoic acid as Coryneform species such as Brevibacterium; Propionibac the only active ingredient or compositions containing a terium acnes Such as P. acnes, P. granulosum and Pavidium; 15 dermatological or pharmaceutical agent and a Synergistic gram-negative bacteria including Proteus and E. coli, gram amount of an aryl 2-acetoxyethanoic acid. The dermatologi positive bacillus and mycobacteria; and Pityrosporum spe cal and pharmaceutical agents include, for example, cies such as P ovale, P orbiculae and Malassezia furfur. clotrima Zole, miconazole, econazole, ketoconazole, Aryl 2-acetoxyethanoic acids may also be incorporated metronidazole, griseofulvin, ciclopiro X, nyStatin, into a food product or into a cosmetic or pharmaceutical polymyxin, dicloxacillin, fluconazole and acyclovir. composition as a preservative to prevent the growth of a microorganism. Preparation of Therapeutic/Prophylactic We have further discovered that aryl 2-acetoxyethanoic Compositions acids can be Synergistic to or can amplify the bioactivity of Aryl 2-acetoxyethanoic acid compositions may be formu a dermatologic or topical agent. For example, Salicylic acid 25 lated in various forms, Such as a Solution, gel, cream, Stick, may be useful as a keratolytic agent for topical treatment of balm, lotion, Spray or powder form. In a typical anhydrous follicular lesions associated with comedones or follicular Solution form, an aryl 2-acetoxyethanoic acid is dissolved in occlusions. Salicylic acid, however, is not therapeutically a mixture of ethanol and propylene glycol. The Solution may effective against acne lesions associated with whiteheads contain the aryl 2-acetoxyethanoic acid in an amount from caused by microbial infections including P. acnes. An ampli about 0.01% to about 99%, with a preferred concentration of fying composition containing Salicylic acid and an effective about 0.05% to about 10%; ethanol in an amount from about amount of an aryl 2-acetoxyethanoic acid has been found to 1% to about 90%, with a preferred concentration of about eradicate or Substantially improve the clearing of both 20% to about 80%; and propylene glycol in an amount from blackhead and whitehead lesions caused by physiologic about 1% to about 60%, with a preferred concentration of factors and microbial infections. 35 about 5% to about 40%. Unless otherwise indicated, all We have further discovered that aryl 2-acetoxyethanoic liquid percentages Stated herein are weight/volume percent. acids can reverse a drug resistance to many dermatologic In the preparation of a composition in powder form, the agents Such as corticosteroids. For example, clobetasol aryl 2-acetoxyethanoic acid is first ground into fine powder propionate, betamethasone dipropionate, betamethasone with mortar and pestle or ball-mill machine, for example. Valerate and triamcinolone acetonide are topically effective 40 The powdered substance is then mixed thoroughly with talc in the improvement of psoriatic lesions. Many patients powder. The concentration of aryl 2-acetoxyethanoic acid however develop drug resistance to continued medications, may range from about 0.01% to about 20%, with a preferred a phenomenon known as tachyphylaxis or drug unrespon concentration of about 0.02% is to about 5%. Unless oth Siveness. The cause for Such drug unresponsiveness is erwise indicated, all Solid percentages Stated herein are unknown. It has been speculated that a receptor molecule for 45 percent by weight of total composition. the corticosteroid might be depleted on chronic use of topical corticosteroid. At the time when the tachyphylaxis To formulate a Synergistic or amplified composition an occurred on continued use of a corticosteroid, a composition aryl 2-acetoxyethanoic acid may be directly incorporated containing an aryl 2-acetoxyethanoic acid was found to into a composition containing a topical agent for cosmetic or reverse Such unresponsiveness, and psoriatic lesions began 50 dermatologic indications. Aqueous formulations are also to improve. possible by dissolving the aryl 2-acetoxyethanoic acid in Dermatologic agents and topical agents of cosmetic or ethanol, for example, then mixing with water. Propylene pharmaceutical Substances may be incorporated into the glycol and other common Solvents may be added to Such composition containing an aryl 2-acetoxyethanoic acid to alcoholic aqueous Solutions. Alternatively, the topical agent amplify the bioactivity for topical treatment of various 55 may be applied Separately, but Substantially cosmetic and dermatologic indications. Topical agents contemporaneously, with the aryl 2-acetoxyethanoic acid. which may be incorporated into the present composition The invention will now be described in more detail with include local analgesics and anesthetics, antiacne agents, reference to the following Specific, non-limiting examples. antibacterial agents, antiyeast agents, antifungal agents, anti EXAMPLE 1. Viral agents, antidermatitis agents, antipruritic (antitch) 60 agents, antiinflammatory agents, antiperSpirants, antipsori The following Strains of microorganisms were used in atic agents, antiaging and antiwrinkle agents, SunScreen and Minimum Inhibitory Concentration (MIC) tests for phenyl Sunblock agents, Skin lightening agents, depigmenting 2-acetoxyethanoic acid in this example and for benzoyl agents, Vitamins, corticosteroids, hormones and retinoids. peroxide, chlorhexidine gluconate and triclosan in the fol Examples of cosmetic and pharmaceutical agents include 65 lowing examples. In total, five Strains were used for S. Salicylic acid, pramoxine, clotrimazole, ketoconazole, aureus, five Strains were used for S. epidermidis, two Strains miconazole, econazole, fluconazole, metronidazole, were used for M. Sedentarius, three strains were used for M. 5,958,975 7 luteus, two Strains were used for B. epidermis, three Strains were used for C. minutissium, one Strain was used for S. marceScens, three Strains were used for P. aeruginosa, four MIC ml Strains were used for E. coli, and thirty-two Strains were used No Lipid Lipid for P. acnes. 1. Staphylococcus aureus 125 >2OOO Antimicrobial effects were determined based on MIC 2. Staphylococcus epidermidis 125 >2OOO Agar Dilution Test utilizing Trypticase Soy Agar II (BBL) 3. Micrococcus Sedentarius 125 >2OOO incorporation plates with and without 10% intralipid (Kabi 4. Micrococcus luteus 125 >2OOO Pharmacia Inc.). Initially, phenyl 2-acetoxyethanoic acid 5. Brevibacterium epidermis 250 >2OOO 6. Corynebacterium minutissium 125 >2OOO was prepared as a 2 mg/ml (0.2%) Solution in water. This 7. Serratia narceScens 1OOO >2OOO Solution with Serial dilution was incorporated into the test 8. Pseudomonas aeruginosa 1OOO >2OOO agar plates. The MIC test gave similar results when the same 9. Escherichia coli 250 >2OOO Species but a different Strain was used. 10. Propionibacterium acnes 62.5 >2OOO

15 The above results show that chlorhexidine gluconate was MIC ml effective against the growth of the above bacteria when no No Lipid Lipid lipid materials were present in the test medium. However, 1. Staphylococcus aureus 500 500 chlorhexidine gluconate was totally ineffective against the 2. Staphylococcus epidermidis 1OOO 1OOO growth of the above bacteria when 10% lipid materials were 3. Micrococcus Sedentarius 500 500 incorporated in the test medium. 4. Micrococcus luteus 1OOO 1OOO 5. Brevibacterium epidermis 1OOO 1OOO EXAMPLE 4 (COMPARATIVE) 6. Corynebacterium minutissium 500 500 7. Serratia narceScens 1OOO 1OOO Under the same test conditions described in Example 1, 8. Pseudomonas aeruginosa 1OOO 1OOO 25 triclosan was prepared as a 10 mg/ml (1%) Solution in water. 9. Escherichia coli 1OOO 1OOO This solution with serial dilution was incorporated into the 10. Propionibacterium acnes 250 250 test agar plates. Typical test results are shown as follows.

The above results show that phenyl 2-acetoxyethanoic MIC (ug/ml acid had inhibitory effects against all of the above bacteria, and the compound at 250 tug/ml (0.025%) concentration was No Lipid Lipid Specifically effective against the growth of P. acnes even in 1. Staphylococcu.S. aureus 156 >1OOOO the presence of 10% lipid materials. 2. Staphylococcus epidermidis 156 SOOO 3. Micrococcus Sedentarius 156 >1OOOO EXAMPLE 2 (COMPARATIVE) 35 4. Micrococcus luteus 156 >1OOOO 5. Brevibacterium epidermis 156 >1OOOO Under the same test conditions described in Example 1, 6. Corynebacterium minutissium 156 >1OOOO 7. Serratia narceScens >1OOOO >1OOOO benzoyl peroxide was prepared as a 2.5 mg/ml (0.25%) 8. Pseudomonas aeruginosa >1OOOO >1OOOO Solution in water. This solution with serial dilution was 9. Escherichia coli 156 >1OOOO incorporated into the test agar plates. Typical test results are 40 10. Propionibacterium acnes 156 >1OOOO shown as follows. The above results show that triclosan was effective MIC ml against the growth of the above bacteria excluding S. marce Scens and P. aeruginosa in the absence of lipid materials. No Lipid Lipid 45 However, triclosan was ineffective against the growth of the 1. Staphylococcus aureus 2500 1250 above bacteria when 10% lipid materials were incorporated 2. Staphylococcus epidermidis 2500 1250 in the test medium. 3. Micrococcus Sedentarius 2500 650 4. Micrococcus luteus 2500 650 EXAMPLE 5 5. Brevibacterium epidermis 2500 1250 50 6. Corynebacterium minutissium 2500 1250 A typical test for prophylactic effect in preventing the 7. Serratia narceScens 72500 1250 development of axillary foul odor was carried out as follows. 8. Pseudomonas aeruginosa 72500 1250 A test composition was prepared by dissolving 0.5 g of 9. Escherichia coli 2500 1250 phenyl 2-ace to Xy ethanoic acid or diphenyl 10. Propionibacterium acnes 2500 625 2-acetoxyethanoic acid in 70 ml of ethanol and 30 ml of 55 propylene glycol. The control vehicle was prepared by The above results show that benzoyl peroxide was mod mixing 70 ml of ethanol and 30 ml of propylene glycol. A erately effective against the growth of the above bacteria human Subject, male, age 71, was instructed to take a shower excluding S. marceScenS and P. aeruginoSa when lipid in the morning using ordinary Soap to clean the body materials were present in the test medium. Surfaces. After the skin was dried, the test composition was 60 topically applied to the left underarm area only. The vehicle EXAMPLE 3 (COMPARATIVE) control was topically applied to the right underarm area. Both underarm areas were monitored by the Subject and at Under the same test conditions described in Example 1, least one other perSon approximately every 8 hours to chlorhexidine gluconate was prepared as a 2 mg/ml (0.2%) determine whether the test composition had any prophylac Solution in water. This solution with serial dilution was 65 tic effect in preventing the development of underarm foul incorporated into the test agar plates. Typical test results are odor in the left axilla as compared to the vehicle alone on the shown as follows. right control armpit. 5,958,975 10 Presence or substantial absence of foul odor, detected by salicylic acid 2% is suitable for topical treatment of infected Smell, was adopted as the criteria for ineffectiveness or skin lesions including papular and pustular acne lesions. effectiveness of the test composition. It was found that while the right control side developed foul odor within hours, the EXAMPLE 9 left underarm did not produce any detectable odor, even after A prophylactic and therapeutic composition containing an 24 hours. This shows that the test composition containing aryl 2-acetoxyethanoic acid and chlorhexidine for topical 0.5% phenyl 2-acetoxyethanoic acid or diphenyl treatment of skin infections and body odors may be formu 2-acetoxyethanoic acid was Substantially effective in pre lated as follows. Phenyl 2-acetoxyethanoic acid 0.3 g and venting the development of axillary foul odor. chlorhexidine 0.1 g were dissolved in a mixture consisting EXAMPLE 6 of ethanol 70 ml, propylene glycol 28.6 ml and nonoxynol-9 1.0 ml. The solution thus obtained had pH 4.6. The com A typical test for axillary antiodor effectiveness was position thus formulated containing phenyl carried out as follows. A human Subject, female, age 62, 2-acetoxyethanoic acid 0.3% and chlorhexidine 0.1% is could not use existing commercial products of antiperSpi Suitable for topical treatment of body odors as well as skin rants or deodorants because of Severe itching and irritation 15 infections including papular and pustular acne lesions. after topical application. After the foul odor developed in both axillae, the Subject was instructed to apply the Same test EXAMPLE 10 composition as Example 5 containing 0.5% phenyl 2-acetoxyethanoic acid or diphenyl 2-acetoxyethanoic acid A prophylactic and therapeutic composition containing an on the left side underarm and the control vehicle on the right aryl 2-acetoxyethanoic acid and three other topical agents Side. Topical applications were made once daily for Several for topical treatment of skin infections may be formulated as days. follows. Phenyl 2-acetoxyethanoic acid 0.9 g, salicylic acid While the right armpit continued to produce foul odor, the 2.0 g, tartaric acid 0.9 g and citric acid 0.9 g were dissolved left underarm ceased emanating any detectable foul odor in a mixture. consisting of ethanol 70 ml, propylene glycol after 1 day. The Subject was instructed at this time to apply 25 24.4 ml and nonoxynol-11 0.9 ml. The solution thus the test composition on the right Side also. The right axilla obtained had pH 2.1. The composition thus formulated ceased to emanate any detectable foul odor after 1 day of containing phenyl 2-acetoxyethanoic acid 0.9%, Salicylic use. This shows that the test composition containing phenyl acid 2%, tartaric acid 0.9% and citric acid 0.9% is Suitable 2-acetoxyethanoic acid or diphenyl 2-acetoxyethanoic acid for topical treatment of skin infections including papular and was topically effective in eradicating the axillary foul odor. pustular acne lesions. EXAMPLE 7 EXAMPLE 11 A typical test for prophylactic effect in preventing the A prophylactic and therapeutic composition containing an aryl 2-acetoxyethanoic acid and other topical agents for development of, as well as treatment of, foot malodor was 35 carried out as follows. A test composition in powder form topical treatment of Skin infections may be formulated as was prepared by mixing 1 g of finely powdered phenyl follows. Phenyl 2-acetoxyethanoic acid or diphenyl 2-acetoxyethanoic acid with 99 g of talc powder. The talc 2-acetoxyethanoic acid 0.9 g., Salicylic acid 2.0 g, tartaric powder alone was used as a control vehicle. acid 0.9 g, citric acid 0.9 g, retinyl acetate 0.9 g, triethyl citrate 20 g and BHT 0.2 g were dissolved in a mixture A human Subject, female, age 23, had persistent foot 40 consisting of ethanol 63.3 ml, propylene glycol 10 ml, and malodor all year round. She had used commercially avail nonoxynol-11 0.9 ml. The composition thus formulated able foot products containing a mixture of undecylenic acid containing aryl 2-acetoxyethanoic acid 0.9%, Salicylic acid and Zinc or calcium undecylenate with partial or little 2%, tartaric acid 0.9%, citric acid 0.9%, retinyl acetate 0.9% Success in controlling the development of foot malodor. On and triethyl citrate 20% is suitable for topical treatment of the first morning, the Subject was instructed to spread the test 45 composition lightly on the left foot and also inside the hose. skin infections including papular and pustular acne lesions. The control vehicle was used on the right foot and inside the EXAMPLE 12 hose. While the right foot developed malodor by the first evening, the left foot produced no detectable malodor. The A topical composition containing 3% aryl Subject was then instructed to apply the test composition on 50 2-acetoxyethanoic acid as the only active ingredient for both feet the Second morning. At the end of the Second day, treatment of nail infections may be formulated as follows: both feet produced no detectable malodor. The same topical phenyl 2-ace to Xy ethanoic acid or diphenyl applications were continued for Several days, complete 2-acetoxyethanoic acid 3 g was dissolved in isopropyl Suppression of malodor was Sustained. This shows that the alcohol 77 ml, butane-1,3-diol 15 ml and nonoxynol-65 ml. test composition containing phenyl 2-acetoxyethanoic acid 55 A Synergistic composition may be formulated as follows: in powder form was topically effective in preventing the phenyl 2-ace to Xy ethanoic acid or diphenyl development of and in treating foot malodor. 2-acetoxyethanoic acid 1 g and clotrimazole 1 g were dissolved in ethanol 78 ml and propylene glycol 20 ml. EXAMPLE 8 The participating Subjects in the present Study were A prophylactic and therapeutic composition containing an 60 instructed to apply twice daily the composition containing aryl 2-acetoxyethanoic acid and Salicylic acid for topical phenyl 2-ace to Xy ethanoic acid or diphenyl treatment of Skin infections may be formulated as follows. 2-acetoxyethanoic acid with or without clotrimazole as an Phenyl 2-acetoxyethanoic acid 1.0 g and Salicylic acid 2.0 g additional antimicrobial agent. Nail infections usually dis were dissolved in a mixture consisting of ethanol 70 ml, appeared within one to Several months of topical application propylene glycol 26 ml and nonoxynol-6 1.0 ml. The solu 65 with the non-Synergistic composition. The Synergistic com tion thus obtained had pH 2.9. The composition thus for position appeared to shorten the period of topical application mulated containing phenyl 2-acetoxyethanoic acid 1% and and Speed-up the healing of diseased nails. 5,958,975 11 12 EXAMPLE 13 participated in a Study to determine whether the composi Compositions for treatment of oral infections may contain tions containing an aryl 2-acetoxyethanoic acid were thera an aryl 2-acetoxyethanoic acid as the only active ingredient. peutically effective for topical treatment of folliculitis and In this case a phenyl 2-acetoxyethanoic acid or diphenyl other skin lesions, nail infections and mucosal infections 2-acetoxyethanoic acid 2% composition was formulated by caused by microbial infections. Scientific and test results are dissolving the active ingredient 2 g in ethanol 78 ml and overviewed as follows. propylene glycol 20 ml. Before use, this composition was I. Antimicrobial Test Ten different species of bacteria were diluted to 0.1% with water by mixing one part of the used in Minimum Inhibitory Concentration (MIC) tests. The composition with 19 parts of water. The treatment involves bacteria include S. aureus, S. epidermidis, M. Sedentarius, oral rinse, wash and gargle by keeping the diluted compo M. luteus, B. epidermis, C. minutissium, S. marceScens, P Sition inside the oral cavity for a few minutes, and then Spit aeruginosa, E. coli, and P. acneS. In addition various Sources out. Such procedure may be repeated twice daily for Several and Strains of these bacteria were also included in the tests, days until the infection is eradicated usually within 5-7 and up to 32 different strains of P. acnes were used. days. The test substance selected from phenyl 15 2-acetoxyethanoic acid, benzoyl peroxide, chlorhexidine A Synergistic composition may be formulated by dissolv gluconate and triclosan was dissolved in water, and the ing phenyl 2-acetoxyethanoic acid or diphenyl Solution with Serial dilution was incorporated into the test 2-acetoxyethanoic acid 1 g and a pharmaceutical agent Such agar plates. The plates containing different concentrations of as ketoconazole or acyclovir 2 g in ethanol 77 ml and test Substance were inoculated with a Strain of bacterium. propylene glycol 20 ml. Before use, this composition was MIC is defined as the lowest concentration of the test mixed with 19 parts of water. Oral treatment was carried out Substance in the plate in which there is no growth of the in the same procedure as the above. microorganism. Phenyl 2-acetoxyethanoic acid showed inhibitory effects EXAMPLE 1.4 against the growth of all ten bacteria tested, with or without Compositions for topical treatment of Vulvar-vaginal 25 the presence of 10% lipid materials. The compound of the infections may contain an aryl 2-acetoxyethanoic acid as the present invention was specifically effective against P. acnes only active ingredient. In this case, phenyl at 0.025% concentration even in the presence of lipid 2-acetoxyethanoic acid or diphenyl 2-acetoxyethanoic acid materials. 0.3 g was dissolved in ethanol 1 ml. The solution thus In Some instances, different Strains of one bacterium obtained was mixed with petrolatum 66 g and mineral oil might have given rise to slightly different inhibitory effects. 32.7 g. The ointment thus prepared may be applied topically In general, however, different Sources or Strains of the same twice daily to the affected areas for a few days to a few Species were found to give basically very similar results. For weeks. example, five Strains of S. epidermis from 5 Sources with A Synergistic composition may be formulated by dissolv numbers Atcc 35984, Atcc 31432, Atcc 14490, Dh 557 and ing phenyl 2-acetoxyethanoic acid or diphenyl 35 Dh 640 gave identical results. Thirty-two different strains of 2-acetoxyethanoic acid 0.1 g and clotrimazole 0.2 g in P. acnes (twenty from acne lesions and the remaining twelve ethanol 2 ml and nonoxynol-6 5 ml. The mixture thus from other Sources) all gave identical results. obtained was mixed with petrolatum 66 g and mineral oil Under the Same test conditions, benzoyl peroxide at 26.7 g. The topical formulation thus prepared may be 0.0625% concentration showed inhibitory effects against M. applied twice daily to the affected area until the infection has 40 Sedentarius, M. lutens, and P. acnes in the presence of 10% Subsided. lipid materials. This antiacne compound was not effective against the growth of all the bacteria tested in the absence of EXAMPLE 1.5 lipid materials. An aryl 2-acetoxyethanoic acid may be incorporated in Chlorhexidine gluconate at 0.02 to 0.05% concentration is 45 used as a general antiseptic on skin and mucous membranes. food products, cosmetic and pharmaceutical formulations Under the same test conditions chlorhexidine gluconate at and industrial preparations as a preservative to prevent the 0.006 to 0.1% concentration was found to be effective growth of microorganism(s). The concentration of an aryl against all the bacteria tested in the absence of lipid mate 2-acetoxyethanoic acid used may range from 0.01% to 1% rials. However, this antiseptic Substance was not effective with a preferred concentration of 0.02% to 0.2%. 50 against the growth of all the bacteria tested in the presence An aryl 2-acetoxyethanoic acid may also be used in of lipid materials. compositions as a routine oral hygiene aid. The concentra Triclosan at 1% concentration is used in liquid and bar tion of the active ingredient may range from 0.01% to 0.5% Soap as a disinfectant and medicated cleanser for acne-prone with preferred concentration of 0.02% to 0.1%. An aryl skin. Under the same test conditions triclosan at 0.0156% 2-acetoxyethanoic acid may also be incorporated into Soaps, 55 concentration was found to be effective against all the Soap bars, Sticks, balms and the like for personal care and bacteria except S. marceScens and P. aeruginosa in the routine hygiene care. The concentrations may range from absence of lipid materials. However, this disinfectant was 0.01% to 1% with preferred concentration of 0.02% to 0.5%. not effective against the growth of all the bacteria tested in Test Results Overview the presence of 10% lipid materials. 60 The above antimicrobial test results show that the phenyl In order to determine the antimicrobial effect of an aryl 2-acetoxyethanoic acid is the most active and effective 2-acetoxyethanoic acid, a Standard test method of Minimum compound against P. acnes with or without the presence of inhibitory Concentration (MIC) against the growth of 10 lipid materials in the test medium. bacteria was used. To determine a prophylactic effect against II. Body Odor the development of, as well as a topical effect in the 65 A. Axillary Foul Odor treatment of, body foul door, eleven human Subjects partici A total of Seven Subjects (four females ages 62, 64, 78, pated in this study. More than twenty human Subjects and 81; three males ages 36, 38 and 68) participated in 5,958,975 13 14 Several Studies. Most of these Subjects could not use existing B. Foot Malodor commercial products of antiperspirants or deodorants A total of six subjects (three females ages 23,35, and 57; because of Severe irritation after topical application. Phenyl three males ages 43, 61 and 70) participated in several 2-acetoxyethanoic acid or diphenyl 2-acetoxyethanoic acid Studies. Most of these participants had used commercially 0.5% concentration and a control vehicle (70 volume 96 available products for foot malodor including those contain ethanol, 30 volume 76 propylene glycol) were prepared in ing a mixture of undecylenic acid and Zinc or calcium one-ounce container bottles according to the examples. The undecylenate without much Success in controlling the devel participating Subjects were instructed to take a shower in the opment of foot malodor. morning using ordinary Soap to clean the body Surfaces. A test composition containing 1% phenyl After the Skin was dried, the test composition containing 2-acetoxyethanoic acid in powder form was prepared by 0.5% aryl 2-acetoxyethanoic acid was topically applied to mixing thoroughly 1 g of finely powdered compound with the left underarm area only. The control vehicle was topi 99 g of talc powder. The talc powder alone was used as a cally applied to the right underarm area. Topical applications control vehicle. The test composition and the control vehicle were repeated 8 hours later. were packaged in one-ounce powder containers. The par Both underarm areas were monitored by the subject and 15 ticipating Subjects were instructed to lightly spread the test at least one other perSon approximately every 8 hours to composition on the bottom of the left foot and inside the determine whether the test composition had any prophylac hose or Sock on the first morning. tic effect in preventing the development of underarm foul The criteria for ineffectiveness or effectiveness of the test odor in the left axilla as compared to the vehicle alone on the composition were based on presence or absence of malodor right control underarm. The criteria for ineffectiveness or as detected by olfactory sense of Smell. Both feet were effectiveness of the test composition were based on presence monitored by the Subject and at least one other perSon in the or absence of foul odor as detected by olfactory Sense of evening. While the right foot developed malodor by the first Smell. It was found in all the participating Subjects that while evening, the left foot produced no detectable malodor in all the right control side developed underarm foul odor by 8 the participating Subjects. hours, the left axilla did not produce any detectable odor, 25 The Subjects were then instructed to apply the test com even after 16 hours. This test result shows that the compo position on both feet the next morning. At the end of the Sition containing 0.5% aryl 2-acetoxyethanoic acid is topi second day, both feet produced no detectable malodor. The cally effective in preventing the development of axillary foul Same topical applications were continued by all the partici odor. pants for Several days to confirm the above results. The axillary antiodor effectiveness was determined as The test results show that the test composition containing follows. The above participating Subjects were instructed to 1% phenyl 2-acetoxyethanoic acid was topically effective in topically apply the test composition containing 0.5% phenyl preventing the development of and was also therapeutically 2-acetoxyethanoic acid or diphenyl 2-acetoxyethanoic acid effective for topical treatment of foot malodor. on the right underarm and discontinue the use of the control III. Folliculitis and Perifolliculitis vehicle after the foul odor had developed. The subjects 35 Nine patients having various degrees of folliculitis and continued to use the same test composition containing 0.5% perifolliculitis participated in this study. A test composition phenyl 2-ace to Xy ethanoic acid or dip in he nyl containing 0.9% phenyl 2-acetoxyethanoic acid or dipnenyl 2-acetoxyethanoic acid on the left underarm. Topical appli 2-acetoxyethanoic acid was prepared by dissolving 0.9 g, cations were repeated 8 hours later. Thereafter topical appli compound in 79.1 ml 2-propanol, 15 ml butane-1,3-diol and cations were made once daily for Several days. In all the 40 5 ml nonOxynol-6. The composition was packaged in one Subjects tested the right axilla ceased to emanate any detect ounce bottles. The patients were instructed to apply the test able is foul odor after 2 to 3 days of topical use. The left composition twice daily on the infected Skin lesions and axilla continued to maintain the condition free of any involved areas. Topical applications were continued up to 8 offensive foul odor. weeks. The results showed that skin lesions of Superficial In another Study the Subjects were instructed not to take 45 folliculitis and perifolliculitis were eradicated or substan a shower in the morning. After the foul odor developed in tially improved after a few days of topical applications. both axillae, the Subjects were instructed to apply the test Deeper lesions of papules were found to be eradicated or a composition containing 0.5% phenyl 2-acetoxyethanoic acid Substantially improved after 4 to 8 weeks of topical appli or diphenyl 2-acetoxyethanoic acid on the left underarm area cations. and the control vehicle on the right underarm area. Topical 50 IV. Therapeutic Response and Amplified Effects applications were made once daily for Several dayS. (a) Acne While the right underarm continued to produce foul odor, Twelve patients having moderate to Severe acne lesions the left underarm diminished in intensity of foul odor after consisting of pustules and papules participated in this study. one to two days of topical application. Usually the left The test composition containing 2% salicylic acid and 1% underarm ceased emanating any detectable foul odor after 1 55 phenyl 2-ace to Xy ethanoic acid or diphenyl day of topical use. The Subjects were instructed at this time 2-acetoxyethanoic acid was prepared by dissolving 2 g to apply the test composition containing 0.5% phenyl Salicylic acid and 1 g aryl 2-acetoxyethanoic acid in 70 ml 2-acetoxyethanoic acid or diphenyl 2-acetoxyethanoic acid ethanol, 26 ml propylene glycol and 1 ml nonoxynol-6 or 1 on the right underarm area also. Topical applications were ml monoxynol-11. made once daily for Several days. The right axilla ceased to 60 The patients were instructed to topically apply the test emanate any detectable foul odor after 1 to 2 days of topical composition twice daily on the affected areas of the skin for Sc. 4 to 8 weeks. Acne lesions were recorded at the beginning The above results show that the composition containing and at the end of 4 weeks and 8 weeks of topical applica 0.5% aryl 2-acetoxyethanoic acid is topically effective in tions. Ten of twelve patients showed substantial reduction in preventing the development of axillary offensive odor and is 65 the number of pustular and papular lesions after 4 to 8 weeks also therapeutically effective for topical treatment of under of topical treatment with the test composition containing arm foul odor. both Salicylic acid and phenyl or diphenyl 2-acetoxyethanoic 5,958,975 15 16 acid. On continued use of the test composition new lesions without departing from the broad inventive concept thereof. of pustules and papules did not appear over the next 8 weeks. It is understood, therefore, that this invention is not limited This indicated that the test composition has a prophylactic to the particular embodiments disclosed, but it is intended to effect in preventing the development of new acne lesions. cover modifications within the Spirit and Scope of the present (b) Psoriasis invention as defined by the appended claims. Psoriasis is not an infection disease but rather a disorder We claim: caused by genetic factors and is a chronic skin disease 1. A method for reversing or preventing tachyphylaxis of affecting approximately 1 to 3% of the population. This pSoriasis to a corticosteroid, comprising topically applying disease is characterized by Silver Scales and thick, dry, red to pSoriatic skin a corticosteroid effective to treat the pSo skin. Although corticosteroids Such as clobetasol propionate, riasis and an amount of an aryl 2-acetoxyethanoic acid betamethasone dipropionate, betamethasone Valerate and effective to reverse or prevent unresponsiveness of the skin triamcinolone acetonide are topically effective in the control to the corticosteroid treatment. of psoriatic lesions, many patients have developed resistance 2. A method according to claim 1, wherein the aryl to continued medications. 2-acetoxyethanoic acid has the chemical Structural formula To determine the therapeutic responsive effect of an aryl 15 2-acetoxyethanoic acid against psoriasis Seven patient par (I) ticipated in this Study. A test composition was prepared by O O dissolving 1 g phenyl 2-acetoxyethanoic acid or diphenyl || || 2-acetoxyethanoic acid in 2 ml ethanol. The Solution thus RRC(OCCH3)COH obtained was mixed wish 60 g petrolatum and 37 g mineral oil. The anhydrous ointment thus formulated was packaged wherein R=an aryl group having 6 to 13 carbon atoms, and in one-ounce jars. R=H or an aryl group having 6 to 13 carbon atoms, Said When the drug unresponsiveness to a corticosteroid acid including Stereoisomers thereof, and free acids or Salt occurred, the participating patients were instructed to apply forms thereof with an organic or inorganic base. in addition the test composition once daily to the lesions on 25 3. A method according to claim 1, wherein when R the left side of the body only. Topical applications of the and/or R2 is an aryl group, the hydrogen atoms of the group corticosteroid were continued twice daily to both sides of the may be Substituted by an entity Selected from the group body. Psoriatic lesions on the left side of the body began to consisting of F, Cl, Br, I, OH, acetoxy, C-Co lower alkyl, improve after one week of additional topical application and C-C lower alkoxy. with the composition containing phenyl 2-acetoxyethanoic 4. A method according to claim 1, wherein the aryl acid or diphenyl 2-acetoxyethanoic acid. While pSoriatic 2-acetoxyethanoic acid is Selected from the group consisting lesions on the right Side of the body remained unresponsive of phenyl 2-ace to Xye thanoic acid, diphenyl to the topical corticosteroid, the lesions on the left side 2-acetoxyethanoic acid and (4-chlorophenyl) started to clear after 3 to 4 weeks of additional topical 2-acetoxyethanoic acid, (2-chlorophenyl) 2-acetoxyethanoic application with the composition containing an aryl 35 acid, and (4-chlorophenyl) (2-chlorophenyl) 2-acetoxyethanoic acid. 2-acetoxyethanoic acid. At this time the patients were instructed to shift the 5. The method according to claim 1, wherein the aryl additional topical application to the lesions on the right side 2-acetoxyethanoic acid is applied in a form Selected from the instead of the left side of the body. The psoriatic lesions on group consisting of Solutions and ointments. the right side of the body began to clear after 3 to 4 weeks 40 6. The method according to claim 5, wherein the aryl of additional topical application with the composition con 2-acetoxyethanoic acid is applied to the body part in an taining aryl 2-acetoxyethanoic acid. anhydrous ointment comprising the aryl 2-acetoxyethanoic We have also found that the test composition containing acid, ethanol, petrolatum and mineral oil. aryl 2-acetoxyethanoic acid could be used in conjunction 7. A method according to claim 1, wherein the aryl with a corticosteroid product at the beginning of topical 45 2-acetoxyethanoic acid is phenyl 2-acetoxyethanoic acid. treatment to prevent the development of tachyphylaxis to 8. A method according to claim 1, wherein the aryl corticosteroid. 2-acetoxyethanoic acid is diphenyl 2-acetoxyethanoic acid. It will be appreciated by those skilled in the art that chances could be made to the embodiments described above k k k k k